Genetic Variant NM_199136.5:c.287C>T (chr7-23689316-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_199136.5(FAM221A):c.287C>T(p.Pro96Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000041 in 1,585,146 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

FAM221A
NM_199136.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65

Publications

0 publications found

Variant links:

Genes affected

FAM221A (HGNC:27977): (family with sequence similarity 221 member A)

FAM221A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM221A	NM_199136.5	MANE Select	c.287C>T	p.Pro96Leu	missense	Exon 3 of 7	NP_954587.2	A4D161-1
FAM221A	NM_001127364.3		c.287C>T	p.Pro96Leu	missense	Exon 3 of 6	NP_001120836.1	A4D161-2
FAM221A	NM_001300932.2		c.113C>T	p.Pro38Leu	missense	Exon 2 of 6	NP_001287861.1	B8ZZQ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM221A	ENST00000344962.9	TSL:1 MANE Select	c.287C>T	p.Pro96Leu	missense	Exon 3 of 7	ENSP00000342576.4	A4D161-1
FAM221A	ENST00000409192.7	TSL:1	c.287C>T	p.Pro96Leu	missense	Exon 3 of 6	ENSP00000386927.3	A4D161-2
FAM221A	ENST00000409994.3	TSL:1	c.113C>T	p.Pro38Leu	missense	Exon 2 of 5	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000676

AC:

AN:

251350

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1432978

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

707434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33080

American (AMR)

AF:

0.0000225

AC:

AN:

44372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25826

East Asian (EAS)

AF:

0.00

AC:

AN:

38928

South Asian (SAS)

AF:

0.000355

AC:

AN:

84540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52980

Middle Eastern (MID)

AF:

0.000586

AC:

AN:

5118

European-Non Finnish (NFE)

AF:

0.0000239

AC:

AN:

1089180

Other (OTH)

AF:

0.0000509

AC:

AN:

58954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000731

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.7

PhyloP100

5.6

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.71

MutPred

0.51

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.27

MPC

0.42

ClinPred

0.92

GERP RS

4.8

Varity_R

0.43

gMVP

0.40

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over